Vasomotor symptoms (VMS), defined as hot flashes and night sweats, are experienced by the majority of women during the menopausal transition. In addition to impacting quality of life, epidemiologic evidence suggests that in some women, VMS characteristics (severity, duration, and timing) may be a clinical marker for underlying physiologic changes associated with cardiovascular risk, such as stroke and myocardial infarction. Whether VMS characteristics are a marker for a pro-thrombotic state and associated with an increased risk of venous thrombosis (VT) is not known, yet VT risk is an excellent candidate phenotype for such a sex-hormone dependent association. The proposed study will be the first to evaluate the association between VMS and thrombotic risk in postmenopausal women by analyzing existing data from the Women's Health Initiative (WHI- HT) Hormone Therapy trials. The first aim evaluates the cross-sectional association between hemostatic factors and the presence of VMS and its severity, duration, and timing. The second aim evaluates prospectively the risk of clinical VT associated with VMS presence and its severity, duration, and timing. The WHI-HT previously enrolled 27,347 postmenopausal women ages 50-79 years of age and at baseline, collected data regarding the presence and severity of VMS. Following a 3-month hormone therapy (HT) washout and prior to any randomization of HT, the WHI also collected blood samples in which a number of hemostatic factors, such as normalized activated protein C sensitivity ratio (nAPCsr), anti-thrombin (AT) and free and total protein S have been measured. VT events were centrally-adjudicated by WHI researchers using standardized criteria. To address aim 1, multiple linear regression will be used to model the association of VMS presence with each hemostatic factor, separately, adjusting for matching variables and confounders. To address aim 2, our primary analyses will assess the association of baseline VMS presence with time-to-VT event (defined as PE or DVT) using Cox Proportional Hazards models. The hypotheses we propose are not currently being investigated by WHI, either in core or ancillary studies. An understanding of VMS as a potential marker for thrombotic risk has important implications for both clinical practice and etiologic understanding. Self- reported VMS may serve as a minimally invasive clinical marker, useful for the identification of women experiencing undetected changes in intermediate thrombotic phenotypes and potentially at an increased risk of VT and other CVD events. An evaluation of VMS as a potential marker for thrombotic risk will further our understanding of both the etiology of VT as well as the physiology of VMS, both of which are in need of better characterization. In addition to addressing our specific aims, this proposed study will provide new evidence for future studies necessary to elucidate the etiology of thrombotic disease in women.